Surrozen Submits IND for SZN-8141, a Bifunctional Wnt Agonist/VEGF Antagonist for Diabetic Macular Edema
核心洞察
Surrozen (搜索) has submitted an Investigational New Drug (IND) application to the FDA for SZN-8141, a bifunctional Wnt agonist and VEGF (搜索) antagonist antibody, for the treatment of diabetic macular edema (搜索) (DME).
SZN-8141 combines Frizzled 4 (搜索) (FZD4)-mediated Wnt agonism with VEGF (搜索) antagonism, and in preclinical models demonstrated superior reductions in neovascularization and vascular leakage versus anti-VEGF monotherapy.
The DUET Phase 1b/2a trial is expected to initiate by year-end 2026, with initial data anticipated in the second half of 2027.
Surrozen (搜索), Inc. (Nasdaq: SRZN), a biotechnology company pioneering Wnt-based therapeutics for sight-threatening ophthalmic conditions, has submitted an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) seeking to evaluate SZN-8141 for the treatment of diabetic macular edema (搜索) (DME). SZN-8141 is a bifunctional antibody that combines Wnt pathway activation with vascular endothelial growth factor (VEGF (搜索)) antagonism in a single molecule.
"We believe SZN-8141 has the potential to offer a differentiated approach to retinal vascular disease by combining two complementary mechanisms, activation of the Wnt pathway and inhibition of VEGF (搜索), in a single molecule," said Craig Parker, Chief Executive Officer of Surrozen (搜索). "By bringing together these mechanisms, SZN-8141 is designed to both address vascular leakage and promote retinal vascular integrity."
Mechanism of Action and Preclinical Evidence
SZN-8141 combines Frizzled 4 (搜索) (FZD4)-mediated Wnt agonism with VEGF (搜索) antagonism, a dual mechanism intended to provide benefits over single-mechanism agents targeting either pathway alone. In preclinical studies, SZN-8141 demonstrated superior biological activity in reducing neovascularization and promoting retinal revascularization compared with either Wnt agonist or anti-VEGF monotherapy in a rodent model of retinal vascular disease. The molecule also demonstrated greater reductions in vascular leakage than anti-VEGF therapy in a rodent model of neovascular age-related macular degeneration (搜索) (wet AMD).
Data generated in preclinical models of retinopathy further demonstrated that SZN-8141 stimulated Wnt signaling and induced normal retinal vessel regrowth while suppressing pathological vessel growth.
The DUET Phase 1b/2a Clinical Trial
SZN-8141 will be evaluated in a Phase 1b/2a clinical trial in DME called DUET, designed to assess safety, tolerability, and early signs of biological and clinical activity. The trial consists of an open-label Phase 1b single-ascending-dose portion enrolling both treatment-naïve and previously treated patients with DME (Part 1), followed by a randomized, double-masked Phase 2a dose-expansion portion in treatment-naïve patients with DME (Part 2).
In Part 1, patients will receive a single intravitreal injection of SZN-8141 and be followed for approximately three months to evaluate safety and tolerability, as well as pharmacokinetics, immunogenicity, and exploratory measures of retinal function and anatomy, including best-corrected visual acuity (BCVA), optical coherence tomography (OCT), OCT angiography (OCT-A), and ultra-widefield fluorescein angiography.
Part 2 is expected to evaluate two dose levels of SZN-8141 compared with Vabysmo (faricimab-svoa) in approximately 60 treatment-naïve patients with DME. Patients are planned to receive three monthly doses followed by an additional four-month follow-up period to assess durability of effect. Key outcome measures include the same functional and anatomic measurements as in Part 1.
Surrozen (搜索) expects to initiate the DUET Phase 1b/2a study in DME patients by year-end 2026, with initial data anticipated in the second half of 2027. The Company is also planning to develop SZN-8141 in neovascular age-related macular degeneration (搜索) and is evaluating development in other retinal vascular diseases.
Treatment Landscape and Differentiation
The current standard of care for diabetic retinopathy (including DME), retinal vein occlusion, and wet AMD is intravitreal administration of anti-VEGF (搜索) therapies, including monotherapies and dual-pathway agents targeting VEGF and Ang-2. In addition, Merck (搜索)'s MK-3000, a FZD4-mediated Wnt agonist monotherapy, has demonstrated proof of concept in DME in a clinical trial. Surrozen (搜索) believes SZN-8141 has the potential to treat multiple retinopathy indications and be differentiated from existing therapies.
Intellectual Property and Corporate Developments
In July 2026, the U.S. Patent Trial and Appeal Board (PTAB) denied institution of Merck (搜索)'s post-grant review petition challenging certain claims of Surrozen (搜索)'s U.S. Patent No. 12,297,278, determining that the petition failed to show a reasonable likelihood of prevailing with respect to the challenged claims. Craig Parker noted that this decision "reinforces our intellectual property position."
In June 2026, Boehringer Ingelheim achieved a development milestone under the SZN-413 license agreement following the initiation of a Phase 1 study. SZN-413 is a bi-specific antibody targeting FZD4-mediated Wnt signaling designed using Surrozen (搜索)'s SWAP technology, currently being developed for retinal diseases by Boehringer Ingelheim.
As of June 30, 2026, Surrozen (搜索) reported cash and cash equivalents of $102.0 million, compared to $106.9 million as of March 31, 2026.